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NCT03744910 | SNCTP000003557

Studie zur Bewertung der Wirksamkeit und Sicherheit der Behandlung des Prüfmedikaments Clazakizumab im Vergleich zu einem Placebo (inaktive Substanz) bei Empfängern von Nierentransplantationen mit chronisch aktiver Antikörper-vermittelter Abstoßung (CABMR)

Data source: BASEC (Imported from 10.12.2019), WHO (Imported from 01.12.2019)
Changed: 03.12.2019
Disease category: Anderes

Brief description of trial (Source of data: BASEC)

Ziel dieser Studie ist es, die Wirksamkeit und Sicherheit der Behandlung mit Clazakizumab im Vergleich zu einem Placebo (inaktive Substanz) bei Empfängern von Nierentransplantationen mit CABMR zu untersuchen. In der Studie wird untersucht, ob Clazakizumab den Funktionsverlust der transplantierten Niere verlangsamen oder verhindern und den Zeitraum verlängern kann, bevor die Patienten wieder zur Dialyse gehen oder eine neue Niere bekommen müssen.

Clazakizumab oder das Placebo wird alle 4 Wochen subkutan (Injektionen unter die Haut) verabreicht.

Die Studie wird aus folgenden Behandlungsperioden bestehen:
- Das Screening-Verfahren beträgt bis zu 6 Wochen. Der Screening-Besuch besteht aus einer Bewertung, um festzustellen, ob die Patienten alle Zulassungsvoraussetzungen für die Teilnahme an der Studie erfüllen.
- Die Behandlungsdauer beträgt bis zu 260 Wochen, wobei die Patienten alle 4 Wochen eine subkutane Injektion (entweder Clazakizumab 12,5 mg / ml oder Placebo 1 ml) erhalten.
- Die Nachbeobachtungszeit beträgt bis zu 5 Monaten nach der letzten Dosis des Prüfpräparats.
Die maximale Studiendauer für einen einzelnen Patienten beträgt ca. 5,5 Jahre.

Health conditions investigated (Source of data: BASEC)

Behandlung einer chronisch aktiven Antikörper-vermittelten Abstoßung bei Patienten mit Nierentransplantationen

Health conditions (Source of data: WHO)

Antibody-mediated Rejection

Rare disease (Source of data: BASEC)

No

Intervention investigated (e.g. drug, therapy or campaign) (Source of data: BASEC)

Die Patienten werden nach dem Zufallsprinzip ausgewählt und erhalten entweder:
Clazakizumab 12,5 mg / ml SC-Injektion einmal alle 4 Wochen für bis zu 260 Wochen oder bis zum Verlust des Allotransplantats oder Tod
oder
- Placebo-1-ml-SC-Injektion alle 4 Wochen bis zu 260 Wochen oder bis zum Verlust des Allotransplantats oder Tod
- Die Patienten müssen auch eine prophylaktische Behandlung (orales Trimethoprim / Sulfamethoxazol 80 mg als Trimethoprim täglich oder 160 mg als Trimethoprim x 3 pro Woche) für PJP (Pneumocystis jiroveci pneumonia) vom Screening-Termin bis einschließlich Woche 52 einnehmen alternative prophylaktische PJP-Therapie beim Screening Sie können nach Ermessen des Prüfarztes verbleiben oder wenn die derzeitige Therapie nicht geeignet ist, sollte Trimethoprim / Sulfamethoxazol mindestens 1 Woche vor V2 begonnen werden. Für den Rest der Studie (> Woche 52) sollte die PJP-Prophylaxe nach Ermessen des Prüfarztes fortgesetzt werden.

Interventions (Source of data: WHO)

Biological: Clazakizumab
Drug: Normal saline

Criteria for participation in trial (Source of data: BASEC)

1. Alter 18-70 Jahre
2. Empfänger von Lebendspender- / verstorbenen Spendernierentransplantaten ≥ 6 Monate ab dem Zeitpunkt
der Transplantation
3. Diagnose von CABMR (gemäß den diagnostischen Kriterien von Banff 2015)

Exclusion criteria (Source of data: BASEC)

1. eGFR <25 mL/min/1.73 m2 or >65 mL/min/1.73 m2 (MDRD4)
2. Vorgeschichte von Magen - Darm - Perforationen, Divertikelerkrankungen oder Divertikulitis oder entzündliche Darmerkrankung
3. Aktive Infektionen, die systemische antimikrobielle Wirkstoffe erfordern und sind ungelöst vor dem Screening

Inclusion/Exclusion Criteria (Source of data: WHO)


Unless specified otherwise, all eligibility criteria time-intervals are assessed with
respect to the screening visit.

1. Age 18-70 years.

2. Living donor/deceased donor kidney transplant recipients =6 months from time of
transplant.

3. Diagnosis of CABMR (according to Banff 2015 diagnostic criteria) to include all of the
following:

- Biopsy-proven CABMR (i.e., chronic glomerulopathy (cg) >0) with/without C4d
staining. Repeat biopsy to be performed if previous biopsy is not within 6 months
of the start of the screening period. The local pathologist's diagnosis will be
reviewed by a central pathologist to confirm eligibility for entry into the
study. Subjects without evidence of chronic tissue injury on light microscopy but
who have glomerular basement membrane double contours on electron microscopy
(cg1a) are eligible.

- Positive for human leukocyte antigen (HLA) DSA (using single-antigen bead based
assays) post-transplant. Local laboratory DSA results will be reviewed by the
central HLA reviewer to confirm eligibility for entry into the study. A single
antigen bead MFI >1,000 will be considered positive. If presence of HLA DSA is
confirmed within 6 months of the start of the screening period, the test does not
need to be repeated for eligibility.

- Note: Treatments for ABMR (including CABMR) or TCMR are not allowed within 3
months of the start of screening (see Exclusion Criterion 3). If a subject has
received one of these treatments at any time prior, a repeat biopsy and repeat
DSA must be performed after halting/completing treatment (to show continuing
CABMR).

4. Written informed consent obtained from subject (or legally acceptable representative)
before any trial-related procedures.

Exclusion Criteria:

1. Participant is unable or unwilling to comply with study procedures in the opinion of
the Investigator.

2. Multi-organ transplant recipient or cell transplant (islet, bone marrow, stem cell)
recipient.

3. Treatment for ABMR (including CABMR) or TCMR within 3 months of the start of
screening.

4. Received T cell depleting agents (e.g., alemtuzumab, anti-thymocyte globulin) within 3
months of the start of screening.

5. Treatment with mTOR inhibitors within 4 weeks of the start of screening.

6. Biopsy showing pure TCMR or advanced interstitial fibrosis (ci3), advanced tubular
atrophy (ct3), vascular fibrous intimal thickening (cv3) or other significant causes
of renal dysfunction (e.g., polyoma BK virus (BKV) nephropathy, glomerulonephritis).

7. Impaired renal function due to disorders in the transplanted allograft (e.g., renal
artery stenosis, hydronephrosis).

8. eGFR 65 mL/min/1.73 m2 (MDRD4).

9. Nephrotic range proteinuria defined as spot urine albumin creatinine ratio (UACR)
=2,200 mg/g (=220 mg/mmol). If spot UACR is above defined limits, repeat test on
separate day to confirm ineligibility (or collect 24-hour urine to confirm nephrotic
range proteinuria (=3.0 g/day)).

10. Pregnant, breastfeeding, or unwillingness to practice highly effective birth control
during the study and for 5 months after last dose of investigational drug.

11. History of anaphylaxis.

12. Abnormal liver function tests (LFTs) (alanine aminotransferase (ALT)/aspartate
aminotransferase (AST)/bilirubin >1.5 x upper limit of normal) or other significant
liver disease.

13. History of active tuberculosis (TB).

14. History of latent TB (e.g., positive QuantiFERON-TB test) without history of active TB
unless subject has completed a full course of prophylactic treatment.

15. History of human immunodeficiency virus (HIV) infection or positive for HIV.

16. Seropositive for hepatitis B surface antigen (HBsAg).

17. Hepatitis C virus (HCV) RNA positive.

18. Known Epstein-Barr virus (EBV) mismatch: donor seropositive, recipient seronegative.

19. History of gastrointestinal perforation, diverticular disease or diverticulitis, or
inflammatory bowel disease.

20. Neutropenia (
Minimum age: 18 Years
Maximum age: 70 Years
Sex: All

Further information on the trial in WHO primary registry

http://www.who.int/trialsearch/Trial2.aspx?TrialID=NCT03744910

Further information on the trial from WHO database (ICTRP)

http://apps.who.int/trialsearch/Trial2.aspx?TrialID=NCT03744910

Further information on trial

Date trial registered

06.11.2018

Incorporation of the first participant

14.10.2019

Recruitment status

Recruiting

Academic title (Source of data: WHO)

A Pivotal Phase 3 Trial to Evaluate the Safety and Efficacy of Clazakizumab for the Treatment of Chronic Active Antibody-mediated Rejection in Kidney Transplant Recipients

Type of trial (Source of data: WHO)

Interventional

Design of the trial (Source of data: WHO)

Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).

Phase (Source of data: WHO)

Phase 3

Primary end point (Source of data: WHO)

Incidence of all cause composite allograft loss

Contact information (Source of data: WHO)

Please refer to primary and secondary sponsors

Trial sites

Trial sites in Switzerland (Source of data: BASEC)

Zürich

Countries (Source of data: WHO)

Australia, Canada, France, Hungary, Netherlands, Spain, United States

Contact for further information on the trial

Details of contact in Switzerland (Source of data: BASEC)

Prof. Dr. Thomas Müller
+41 44 255 27 75
Thomas.Mueller@usz.ch

Contact for general information (Source of data: WHO)

Edward Chong, MBChB, MRCP
Vitaeris INC

Contact for scientific information (Source of data: WHO)

Head Project Management and Clinical Operations
844-448-2580
chemise.overton@vitaerisbio.com

Principal Sponsor/Investigator

Principal sponsor (Source of data: WHO)

Vitaeris INC

Additional sponsors (Source of data : WHO)

ICON Clinical Research

Further trial identification numbers

BASEC ID (Source of data: BASEC)

2019-01145

Secondary ID (Source of data: WHO)

VKTX01